Oxygen radical detoxification enzymes in doxorubicin-sensitive and -resistant P388 murine leukemia cells
One of the proposed mechanisms for the cytotoxic effects of anthracycline compounds suggests that the effect is mediated through the formation of intracellular superoxide radicals. It is therefore possible that doxorubicin resistance is associated with increased intracellular enzyme capacity to convert these superoxide radicals to inactive metabolites. We have measured the relative activities of superoxide dismutase, glutathione peroxidase, and catalase in P388 mouse leukemia cells and in a doxorubicin-resistant subline. Since oxygen-reactive metabolites also play a role in mediating the cytotoxicity of ionizing radiation, the radiosensitivity of both cell lines was also studied. No significant differences in superoxide dismutase activity between these cell lines was observed, indicating that they have a similar capacity to convert superoxide anion radicals to hydrogen peroxide. P388 cells that are resistant to doxorubicin have 1.5 times the glutathione content and 1.5 times the activity of glutathione peroxidase measured in drug-sensitive P388 cells. However, incubation with 1-chloro-2,4-dinitrobenzene, which covalently binds glutathione, had no effect on the sensitivity of either cell line to doxorubicin. Measured catalase activity in drug-resistant P388 cells was one-third of the activity measured in doxorubicin-sensitive P388 cells. The activity of this enzyme was much higher than that of glutathione peroxidase in terms of H/sub 2/O/sub 2/ deactivation in both cell lines. It is therefore unlikely that doxorubicin-resistant P388 cells have an increased ability to detoxify reactive oxygen metabolites when compared to drug-sensitive cells. Doxorubicin-resistant P388 cells were significantly more sensitive to X-irradiation than were drug-sensitive P388 cells. These observations suggest that the difference in catalase activity in these cell lines may be associated with the observed differences in radiosensitivity.
- Research Organization:
- Department of Radiation and Clinical Oncology, Hadassah University Hospital, Jerusalem, Israel
- OSTI ID:
- 6879054
- Journal Information:
- Cancer Res.; (United States), Vol. 44:5
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CATALASE
ENZYME ACTIVITY
SUPEROXIDE DISMUTASE
SUPEROXIDE RADICALS
BIOLOGICAL EFFECTS
CELL CULTURES
DOXORUBICIN
LEUKEMIA
LEUKOCYTES
MICE
RADIOSENSITIVITY
X RADIATION
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTINEOPLASTIC DRUGS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOXYLIC ACIDS
DISEASES
DRUGS
ELECTROMAGNETIC RADIATION
ENZYMES
HEMIC DISEASES
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
IONIZING RADIATIONS
MAMMALS
MATERIALS
NEOPLASMS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDOREDUCTASES
PEROXIDASES
PORPHYRINS
RADIATIONS
RADICALS
RODENTS
VERTEBRATES
560121* - Radiation Effects on Cells- External Source- (-1987)
560301 - Chemicals Metabolism & Toxicology- Cells- (-1987)